chr18-756721-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005433.4(YES1):c.107C>T(p.Pro36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,614,164 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 5 hom. )
Consequence
YES1
NM_005433.4 missense
NM_005433.4 missense
Scores
1
13
Clinical Significance
Conservation
PhyloP100: 1.93
Genes affected
YES1 (HGNC:12841): (YES proto-oncogene 1, Src family tyrosine kinase) This gene is the cellular homolog of the Yamaguchi sarcoma virus oncogene. The encoded protein has tyrosine kinase activity and belongs to the src family of proteins. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.018693894).
BS2
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
YES1 | NM_005433.4 | c.107C>T | p.Pro36Leu | missense_variant | 2/12 | ENST00000314574.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
YES1 | ENST00000314574.5 | c.107C>T | p.Pro36Leu | missense_variant | 2/12 | 1 | NM_005433.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000247 AC: 62AN: 251488Hom.: 3 AF XY: 0.000324 AC XY: 44AN XY: 135918
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GnomAD4 exome AF: 0.000142 AC: 207AN: 1461884Hom.: 5 Cov.: 31 AF XY: 0.000195 AC XY: 142AN XY: 727242
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74454
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 20, 2021 | The c.107C>T (p.P36L) alteration is located in exon 2 (coding exon 1) of the YES1 gene. This alteration results from a C to T substitution at nucleotide position 107, causing the proline (P) at amino acid position 36 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
Sift4G
Uncertain
D;D;D
Polyphen
0.010
.;B;B
Vest4
MutPred
0.22
.;Loss of glycosylation at T37 (P = 0.0709);Loss of glycosylation at T37 (P = 0.0709);
MVP
MPC
0.30
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at